English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Anti-PD-1 immunotherapy has recently shown tremendous success for the treatment of several aggressive cancers. However, variability and unpredictability in treatment outcome have been observed, and are thought to be driven by patient-specific biology and interactions of the patient’s immune system with the tumor. Here we develop an integrative systems biology and machine learning approach, built around clinical data, to predict patient response to anti-PD-1 immunotherapy and to improve the response rate. Using this approach, we determine biomarkers of patient response and identify potential mechanisms of drug resistance. We develop systems biology informed neural networks (SBINN) to calculate patient-specific kinetic parameter values and to predict clinical outcome. We show how transfer learning can be leveraged with simulated clinical data to significantly improve the response prediction accuracy of the SBINN. Further, we identify novel drug combinations and optimize the treatment protocol for triple combination therapy consisting of IL-6 inhibition, recombinant IL-12, and anti-PD-1 immunotherapy in order to maximize patient response. We also find unexpected differences in protein expression levels between response phenotypes which complement recent clinical findings. Our approach has the potential to aid in the development of targeted experiments for patient drug screening as well as identify novel therapeutic targets.

Systems biology informed neural networks (SBINN) predict response and novel combinations for PD-1 checkpoint blockade